The purpose of this application for a Center of Biomedical Research Excellence (COBRE) is to foster health-related research and increase the competitiveness of junior, unfunded investigators at the Birth Defects Center at the UL School of Dentistry for independent funding. If funded, this COBRE will augment and strengthen the biomedical research capacity at the Birth Defects Center through provision of flexible support to expand and develop biomedical faculty research capability. The program is led by an established biomedical research scientist, well recognized for his extensive expertise central to the research theme of the proposal. The application seeks support for junior investigators from several complementary disciplines, each of whom will be mentored by an established, well-funded senior biomedical research faculty member, recognized for his/her scientific expertise in the area of the junior investigator's research proposal. This approach is a critical assurance of success of this initiative. This application represents an integrated series of studies focusing on two common themes - molecular mechanisms of birth defects and cellular signal transduction - that encompass a number of diverse scientific disciplines. Faculty from three different departments in the Schools of Dentistry and Medicine, representing a multiplicity of scientific disciplines, present a multifunctional approach to questions of the molecular basis of developmental anomalies. This application, if funded, will substantially enhance the development of five young investigators with outstanding potential to develop into competitive, independent and collaborative investigators. A detailed plan for their research career development has been formulated, expectations and goals for achieving extramural support is outlined, the extent of departmental and university support provided to these junior faculty is substantial, clear and tangible evidence of institutional commitment has been documented, and sufficient and adequate space and equipment resources for the conduct of the proposed studies exists.